Lithium Hydroxide → 1-[7-(2-Chloro-6-fluorobenzyl)-1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl]piperidine-3-carboxylic acid

HRID 1727032Notes

Reaction equation

HRID 1727032 reaction equation
[Cl:1][C:2]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[C:3]=1[CH2:4][N:5]1[C:13]2[C:12](=[O:14])[N:11]([CH3:15])[C:10](=[O:16])[N:9]([CH3:17])[C:8]=2[N:7]=[C:6]1[N:18]1[CH2:23][CH2:22][CH2:21][CH:20]([C:24]([O:26]CC)=[O:25])[CH2:19]1.[Li+].[OH-]>C1COCC1.O>[Cl:1][C:2]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[C:3]=1[CH2:4][N:5]1[C:13]2[C:12](=[O:14])[N:11]([CH3:15])[C:10](=[O:16])[N:9]([CH3:17])[C:8]=2[N:7]=[C:6]1[N:18]1[CH2:23][CH2:22][CH2:21][CH:20]([C:24]([OH:26])=[O:25])[CH2:19]1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 57565596Ethyl 1-[7-(2-chloro-6-fluorobenzyl)-1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl]piperidine-3-carboxylate

Product 1

HCID 100038741-[7-(2-Chloro-6-fluorobenzyl)-1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl]piperidine-3-carboxylic acidYield 103.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of ethyl 1-[7-(2-chloro-6-fluorobenzyl)-1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl]piperidine-3-carboxylate (5.0 g, 10.5 mmol) in 75 mL THF and 25 mL H2O at room temperature was treated with solid LiOH (1.8 g, 43.9 mmol). After stirring overnight the THF was removed under reduced pressure, and the residue was diluted with H2O. The aqueous layer was acidified to pH 4, and the aqueous layer was extracted with CH2Cl2. The combined extracts were concentrated under reduced pressure to give 4.9 g (>99% yield) of the title compound: 1H NMR (CDCl3, 400 MHz) δ7.18 (dt, 2H, J=8.1, 5.7), 7.14 (t, 1H, J=7.6), 6.98-6.90 (m, 1H), 5.57 (AB quartet, 2H, J=15.7, 5.7), 3.51 (s, 3H), 3.42 (dd, 1H, J=12.6, 4.0), 3.30 (s, 3H), 3.20-3.05 (m, 2 H), 2.94-2.83 (m, 1H), 2.59-2.47 (m, 1H), 2.03-1.93 (m, 1H), 1.75-1.40 (m, 3H); LRMS (ESI) m/z 450 (M+H+); TLC (hexanes:EtOAc/1:1) Rf=0.10.

Workup

  1. customwas removed under reduced pressure
  2. additionthe residue was diluted with H2O
  3. extractionthe aqueous layer was extracted with CH2Cl2
  4. concentrationThe combined extracts were concentrated under reduced pressure

Sources & evidence

ORD record
ord-c4ee5e387fc04a8f9ff27d4f2b2b53be
Source dataset
uspto-grants-2009_02
Patent number
US07495004B2

Reaction notes

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